(a) Field of the Invention
This invention relates to novel 1,4,5,6-tetrahydropyrimidine derivatives, to therapeutically acceptable salts thereof, to processes for their preparation, to methods for using the derivatives and to compositions of the derivatives.
More specifically, the present invention relates to novel 1,4,5,6-tetrahydropyrimidine derivatives having a phenyl or substituted phenyl at positions 1 and 6 and in addition being further substituted at position 2. These derivatives are useful as diuretic and saluretic agents without appreciably affecting potassium excretion in a mammal at dosages which do not elicit undesirable side effects.
(b) Description of the Prior Art
A rather large number of reports dealing with 1,4,5,6-tetrahydropyrimidine derivatives are available. More specifically, a number of phenyl substituted 1,4,5,6-tetrahydropyrimidine derivatives have been reported. For example, the report of G. S. Skinner and P. R. Wunz, J. Amer. Chem. Soc., 73, 3814 (1951) discloses 2-phenyl, 2-benzyl and 2-phenylethyl derivatives having pressor activity and the report of J. A. Faust et al., J. Org. Chem., 26, 4044 (1961) discloses 2-(halobenzyl) derivatives having pressor, adrenolytic and sympatholytic activities. Still other examples are the following reports disclosing other phenyl substituted 1,4,5,6-tetrahydropyrimidine derivatives: H. M. Blatter, U.S. Pat. No. 3,332,948, issued July 25, 1967 disclosing 1-(substituted phenyl) derivatives having diuretic and natriuretic activities, and A. C. White and R. M. Black, U.S. Pat. No. 3,926,994, issued Dec. 16, 1975 disclosing 2-benzyl or 2-(substituted benzyl) derivatives having hypoglycaemic, diuretic, antiinflammatory and cardiovascular activities.
The compounds of the present invention are structurally different from the prior art compounds by having a phenyl or substituted phenyl at positions 1 and 6 on the 1,4,5,6-tetrahydropyrimidine ring as well as being substituted at position 2. In addition, the compounds of this invention are prepared using phosphorus oxychloride, a dehydrating agent previously not employed for the preparation of 1,4,5,6-tetrahydropyrimidines,